benzyl N-[(2S)-1-[[(2S)-4-(2-benzylhydrazinyl)-3,4-dioxo-1-phenylbutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: benzyl N-[(2S)-1-[[(2S)-4-(2-benzylhydrazinyl)-3,4-dioxo-1-phenylbutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate
• 化学式: C₃₁H₃₆N₄O₅
• 分子量: 544.651
• InChiKey: DCGUEZDXCJPGNO-SVBPBHIXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  40
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N'N'-(benzyl)(tert-butyloxycarbonylamino)-3(S)-(N-Cbz-leucylamino)-4-phenyl-2-oxobutanoic acid hydrazide 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 以90%的产率得到benzyl N-[(2S)-1-[[(2S)-4-(2-benzylhydrazinyl)-3,4-dioxo-1-phenylbutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate
  参考文献：
  名称：

  Design, Synthesis, Molecular Modeling Studies, and Calpain Inhibitory Activity of Novel α-Ketoamides Incorporating Polar Residues at the P₁‘-Position

  摘要：

  A series of novel alpha-ketoamides incorporating stereoisomeric residues with different electronic properties at the P-1'-position were synthesized to study the electronic requirements for inhibitor binding to the S-1'-subsite of calpain I. The results of the study suggested the presence of an acidic amino acid residue at the S-1'-subsite of calpain I. For example, ester la (CbZ-L-Leu-L-Phe-CO-D-Phe-OMe) was over 450-fold more potent than its carboxylic acid derivative 2a (Cbz-L-Leu-L-Phe-CO-D-Phe-OH). Additionally, amidino derivative 3a (CbZ-L-Leu-L-Phe-CONH-D-CH[C(NH)NH2]Bn) was about 6000-fold more potent than 2a. Furthermore, 4a (Cbz-L-Leu-L-Phe-CONHCH2Bn) was 12-fold less potent than its aza analogue 4b (CbZ-L-Leu-L-Phe-CONHNHBn). The results are consistent with the presence of an acidic amino acid residue at the S-1'-subsite of calpain I. The acidic amino acid residue was found to be Glu261 via molecular modeling studies.

  DOI：

  10.1021/jm0301336